Overview of Systemic Treatment Indications for Pediatric Atopic Dermatitis

Raj Chovatiya, MD, PhD: That’s a very natural transition to talking about what we experience, not only with the past 5 years, but even in the past few months, in terms of the big stuff that’s been happening with atopic dermatitis. I’ll highlight a couple of those big advancements, and maybe we can break them down a little bit for our pediatric population as well. The big ones I’m thinking about are topical ruxolitinib; oral upadacitinib; oral abrocitinib, though its indication is for 18 and up even though it was studied in younger ages; and then of course dupilumab, which we’ll spend a little more time talking about, given some recent advancements in taking it down to ages of infancy.

In the case of topical ruxolitinib, this is a cream that utilizes ruxolitinib, a previously oral JAK [Janus kinase] inhibitor. For those who might not be familiar with JAK inhibitors, the way I like to think about them is a family of serve signaling proteins that are on the inside of the cell, attached to all your favorite receptors that you think about when it comes to biologics, like IL-4, IL-13 and things like that. The way that these medications work is they’re tiny molecules that go into the cell and they can actually inhibit JAK signaling across a lot of different signals. It’s one of the reasons they’re so powerful and they can work so quickly. That seems to be one of the hallmarks we think about with the class. In the case of topical ruxolitinib, this was approved for use in adolescents and adults, all the way down to 12 years old. It’s typically used twice daily for active areas of mild to moderate atopic dermatitis.¼In terms of the TRuE-AD1 and AD2 clinical trials, we’ll talk about that in a little bit. They broke down exactly how this works in terms of itch and lesion clearance as well.

In the case of upadacitinib, this is an oral JAK inhibitor. It’s more JAK1 selective, and that one seems to be the more important JAK protein for a lot of the signaling when we think about atopic dermatitis. This one is also 12 years of age and up. It’s a once-daily oral treatment. It comes in 15 and 30 mg doses, so there is a low dose and a high dose, giving you some flexibility for your patients. This one typically is going to be one you’re thinking about after patients have not had an adequate response to some systemic therapy. This is exactly how it is in the indication. A systemic therapy could include oral steroids, an oral immunosuppressive agent, or a biologic therapy. This is for someone who’s tried one of those things first. I failed to mention, in the case of topical ruxolitinib, that this would be after somebody has had an inadequate response to topical corticosteroids. In the case of abrocitinib, I’ll just mention it here very briefly. It has similar indications to upadacitinib. Access is only 18 years and up. It’s again a more JAK1 selective, and again we’re usually thinking about it after somebody’s had an inadequate response to another systemic therapy.

Finally, in the case of dupilumab, this is a biologic therapy. This is an antibody-based molecule as opposed to a small molecule. It binds the shared receptors subunit that IL-4 and IL-13 share—two really important signals when we think about the pathophysiology of disease. This one really is first-line systemic therapy for somebody who’s had an inadequate response to topical therapy. Until recently it was approved for kids, and now it’s approved down to 6 months of age and up. This is an approved therapy at a variety of different dosing intervals and regimens.

Transcript Edited for Clarity